Histologic Remission (NANCY Index) is Superior to Endoscopic Mucosal Healing in Predicting Relapse Free Survival in Patients With Ulcerative Colitis in Clinical and Endoscopic Remission.

BACKGROUND: Histologic activity is recognized as an important predictor of relapse in ulcerative colitis (UC) patients. Current treatment targets aim at mucosal healing; however, many patients continue to have histologic activity. GOALS: The aim was to assess histologic activity using the validated Nancy histologic index (NHI) score as a predictor of future relapse amongst UC patients in endoscopic and clinical remission. STUDY: In this retrospective cohort study, UC patients in clinical and endoscopic remission at a single tertiary center between 2015 and 2018, who underwent a surveillance colonoscopy were included. Clinical remission was defined by partial Mayo score (MSp) <2, and endoscopic remission was defined by Mayo endoscopic subscore (MES) ≤1. Histologic remission was defined by NHI <2. Predictive factors associated with the primary endpoint of clinical relapse were analyzed. RESULTS: A total of 74 of 184 UC patients were included in the study. Amongst this cohort, 33 patients (45%) demonstrated histologic activity (NHI >1) at enrollment. The median follow-up time was 42 months (interquartile range: 26 to 63 mo) with median relapse free period of 30 months (interquartile range: 18 to 48 mo). Kaplan-Meier analysis demonstrated patients with MES 0 ( P =0.02) and histologic remission ( P <0.0001) had significantly longer relapse free survival. On multivariate analysis only histologic activity remained an independent risk factor of future clinical relapse (hazard ratio: 4.36, confidence interval: 1.68-11.27, P =0.002). CONCLUSION: Histologic remission using the NHI independently predicts significantly longer relapse free survival and may be a superior therapeutic target than endoscopic remission.

A pilot randomised clinical trial of 670 nm red light for reducing retinopathy of prematurity.

BACKGROUND: Photobiomodulation by 670 nm red light in animal models reduced severity of ROP and improved survival. This pilot randomised controlled trial aimed to provide data on 670 nm red light exposure for prevention of ROP and survival for a larger randomised trial. METHODS: Neonates <30 weeks gestation or <1150 g at birth were randomised to receive 670 nm for 15 min (9 J/cm2) daily until 34 weeks corrected age. DATA COLLECTED: placental pathology, growth, days of respiratory support and oxygen, bronchopulmonary dysplasia, patent ductus arteriosus, necrotising enterocolitis, sepsis, worst stage of ROP, need for laser treatment, and survival. RESULTS: Eighty-six neonates enrolled-45 no red light; 41 red light. There was no difference in severity of ROP (<27 weeks-p = 0.463; ≥27 weeks-p = 0.558) or requirement for laser treatment (<27 weeks-p = 1.00; ≥27 weeks-no laser treatment in either group). Survival in 670 nm red light treatment group was 100% (41/41) vs 89% (40/45) in untreated infants (p = 0.057). CONCLUSION: Randomisation to receive 670 nm red light within 24-48 h after birth is feasible. Although no improvement in ROP or survivability was observed, further testing into the dosage and delivery for this potential therapy are required.

ANALYSIS OF TIME TO FAILURE AFTER RETINAL DETACHMENT SURGERY.

PURPOSE: To present the distribution of time to retinal redetachment in eyes undergoing retinal detachment surgery, using a method for adjusting time to outcome in eyes with silicone oil or heavy liquid tamponade ("oil-filled eyes"). METHODS: Data from two Australian centers were used. Adjusted time to outcome was measured from the date of tamponade removal in oil-filled eyes, unless failure was diagnosed with tamponade in situ. RESULTS: 188/1257 failures were identified (15.0%). Using unadjusted time to outcome, failures in oil-filled eyes occurred later than non-oil-filled eyes (median time to failure 57 vs. 28 days, P < 0.001). After adjustment, the distribution of time to failure was similar for oil-filled and non-oil-filled eyes (median 25 vs. 28 days, P = 0.68). Larger detachments, eyes with ≥Grade B proliferative vitreoretinopathy and eyes receiving surgery for recurrent detachments were more likely to fail, but the time to failure was similar regardless of risk. CONCLUSION: Adjustment of time to outcome resulted in a similar distribution of time to failure in oil-filled and non-oil filled eyes and was similar in low- and high-risk eyes. The use of adjusted time to outcome will support consistent collection and interpretation of outcomes across different jurisdictions where time to oil removal may vary.

Smoking in the family is most predictive of the development of childhood asthma in preterm babies <30 weeks gestation: Results of the Respiratory Outcomes Study 2 (RESPOS2).

OBJECTIVES: The Respiratory Outcomes Study 2 (RESPOS2) investigated the relationship between neonatal outcomes (specifically, chronic lung disease [CLD]) and environmental factors on the development of asthma and atopic outcomes at primary school age for preterm babies (PBs) <30 weeks gestational age (GA). METHODS: The study included all surviving PBs <30 weeks GA admitted to the Neonatal Intensive Care Unit at Canberra Hospital, Australian Capital Territory between 2007 and 2009. Parents were sent a questionnaire regarding asthma and atopy symptoms when the PBs were aged 5-7 years old. Data were compared based on CLD status. RESULTS: There were 103 PBs included in the study with a 68.9% response rate to the respiratory questionnaire (71/103). Of these PBs, 15/71 (21.1%) received a diagnosis of CLD. There were no significant differences with regards to asthma, hay fever or eczema in PBs either with or without CLD. The most significant predictor for the development of asthma was smoking in the family (Odds Ratio [OR]: 11.66, 95% Confidence Interval [CI]: 2.01-67.56) with a trend toward significance for family history of asthma (OR: 3.83, 95% CI: 0.85-17.25). CONCLUSION: The RESPOS2 has confirmed previous reports that CLD in PBs <30 weeks GA is not associated with the development of childhood asthma, hay fever or eczema. In our group of PBs, the strongest predictor of the development of asthma was smoking in the family.

Increased use of heated humidified high flow nasal cannula is associated with longer oxygen requirements.

AIM: There has been an increased use of heated humidified high flow nasal canula (HFNC) in premature babies (PBs) admitted to our neonatal unit. The aim of this study is to identify clinical characteristics in PBs < 29 weeks gestational age (GA) that distinguish between those who did not or did receive HFNC. METHODS: This study compared prospectively collected data from 2010 to 2012. Comparisons were undertaken between PBs<29 weeks GA who received continuous positive airway pressure (CPAP: 44/72 (61.1%)) to those who received both CPAP and HFNC (28/72 (38.9%)). Data were analysed using general linear models. RESULTS: There were no significant differences in baseline characteristics between the groups (GA: 27.6 ± 1.1 vs. 27.5 ± 1.1 (weeks), birth weight: 1066 ± 209 vs. 1057 ± 304 (grams) respectively). When analysing outcome measures with multivariate analysis, we found the corrected GA to cease CPAP and oxygen were significantly longer in the HFNC group (31.2 ± 2.1 vs. 32.7 ± 2.0 weeks, P = 0.01 and 32.8 ± 3.5 vs. 36.5 ± 2.8 weeks, P < 0.0001 respectively). CONCLUSIONS: Increased use of HFNC has been associated with increased oxygen requirements. These findings highlight the need to review the use of HFNC in small PBs.

Paediatric Staphylococcus aureus bacteraemia: A single-centre retrospective cohort.

AIM: We aimed to describe the clinical epidemiology of Staphylococcus aureus bacteraemia (SAB) at a large, tertiary/quaternary children's hospital in Australia. METHODS: We performed a retrospective chart review of SAB cases at the Children's Hospital at Westmead (CHW) over 5 years; 2006-2011. We compared frequency, clinical profile and outcomes of SAB with published data from CHW; 1994-1998. We compared health-care associated with community-associated (HCA-SAB and CA-SAB; defined epidemiologically) and methicillin-resistant with methicillin susceptible S. aureus (MRSA and MSSA). RESULTS: We identified 174 episodes of paediatric SAB with an average annual admission rate of 1.3/1000 which has not increased compared with a decade earlier. Half of the cases (49%) were CA-SAB; 18% were MRSA. The proportion of CA-MRSA bacteraemia (22%) has increased. The proportion of SAB associated with central venous access devices (CVADs; 40%) has increased. CA-SAB cases were more likely to present with a tissue focus of disease (e.g. osteo-articular, pneumonia) and often required surgery. HCA-SAB less frequently required surgery, a minority is MRSA, and vascular device intervention (removal, sterilisation) is common. Six cases (4%) of infective endocarditis (IE) were identified; three with a history of congenital heart disease, two with CVADs in situ. There were no deaths in this cohort. CONCLUSIONS: Over an 18-year period, the proportion of SAB due to CA-MRSA and SAB associated with CVADs has increased. Categorisation of SAB as HCA and CA reveals two broad phenotypes of paediatric SAB. SAB in children is infrequently associated with IE. The health-care burden of paediatric SAB is considerable', but mortality is low.

Symptom-to-Balloon Time is a Strong Predictor of Adverse Events Following Primary Percutaneous Coronary Intervention: Results From the Australian Capital Territory PCI Registry.

BACKGROUND: Notwithstanding improvements in door-to-balloon time, adverse event rates after primary PCI have remained steady. We analysed the effect of symptom-to-balloon (STB) time, a reflection of total ischaemic time, on major adverse cardiovascular events (MACE) and explored predictors of prolonged STB time. METHODS: The study population included 1002 consecutive patients (22.4% women) with a mean age of 62.3±13.2 years, who underwent primary PCI during 2008-2014. Groups were compared for STB ≤ and >240min. Primary endpoint was one-year MACE, a composite of death, reinfarction, stent thrombosis or target vessel revascularisation. RESULTS: Symptom-to-balloon time was available in 893 patients of which 588 (65.8%) had STB ≤240min and 305 (34.2%) had STB >240min. The incidence of one-year MACE increased significantly in a stepwise manner with increasing STB time (p for trend=0.003). Symptom-to-balloon time was an independent predictor of one-year MACE along with age >70 years, final TIMI flow <3, three vessel disease, cardiogenic shock and out-of-hospital cardiac arrest. We also performed a multivariate analysis to determine predictors of delayed treatment. Predictors of STB time >240min were age >70 years, female gender, diabetes, absence of prehospital catheter laboratory activation and presentation to a non-PCI centre. CONCLUSION: Incidence of MACE was strongly correlated with STB time and STB time was an independent predictor of MACE. We have identified specific subgroups with prolonged STB times (age >70, female gender, diabetes, absence of prehospital activation and presentation to a non-PCI centre). This information should inform future studies and strategies to minimise delays in these subgroups for improved outcomes.

The Effect of Postoperative Face-Down Positioning and of Long- versus Short-Acting Gas in Macular Hole Surgery: Results of a Registry-Based Study.

PURPOSE: To determine whether sulfur hexafluoride (SF6) gas is noninferior to longer-acting gases in macular hole surgery and whether withholding postoperative face-down positioning (FDP) is noninferior to FDP. DESIGN: Registry-style, prospective, nonrandomized, observational cohort study. PARTICIPANTS: Patients with idiopathic macular holes undergoing primary surgery. METHODS: Surgeons were invited to submit clinical details of all macular hole cases receiving surgery. Baseline demographic and clinical information were collected, as well as details of surgical intervention and postoperative posturing advice. Primary follow-up data were collected 3 months postoperatively. MAIN OUTCOME MEASURES: Macular hole closure at 3 months. A noninferiority approach was used, with a noninferiority margin set at 5% decreased frequency of success. RESULTS: A total of 2456 eyes of 2367 patients were included in the study. Outcomes were available in 94.9% of cases (2330/2456). The rate of macular hole closure was 95.0% (2214/2330). Sulfur hexafluoride gas was found to be noninferior to longer-acting gases (95% confidence interval [CI] for adjusted effect on success, -1.76 to +2.25), and noninferiority was demonstrated regardless of macular hole size. Although withholding FDP was found to be noninferior to FDP for the study population as a whole (95% CI for adjusted effect on success, -4.21 to +0.64), the result was inconclusive in holes >400 µm in diameter (95% CI, -9.31 to +1.04). Lack of internal limiting membrane (ILM) peel, increasing hole size, hole duration ≥9 months, increasing age, and 20-gauge surgery all were associated with lower odds of success. Vitreous attachment to the hole margin was not associated with outcome when corrected for hole size, and combined phacovitrectomy surgery was not observed to affect the odds of success in phakic eyes. CONCLUSIONS: Sulfur hexafluoride gas tamponade was noninferior to longer-acting gases in the surgical management of macular hole. Withholding FDP was noninferior to FDP in holes ≤400 µm in diameter. In holes >400 µm in diameter, noninferiority of withholding FDP could not be concluded. We would advise caution if posturing is withheld in this group on the basis of the results of this study and of others.

CeasIng Cpap At standarD criteriA (CICADA): predicting a successful outcome.

This is a retrospective analysis of a multicentre randomised controlled trial (RCT) where we concluded that CeasIng Cpap At standerD criteriA (CICADA) in premature babies (PBs) <30 weeks gestational age (GA) was the significantly better method of ceasing CPAP. To identify factors that may influence the number of attempts to cease CPAP, we reviewed the records of 50 PBs from the RCT who used the CICADA method. PBs were grouped according to number of attempts to cease CPAP (fast group ≤2 attempts and slow group >2 attempts to cease CPAP). There were 26 (fast group) and 24 (slow group) PBs included in the analysis. Results showed significant differences in mean GA (27.8 ± 0.3 vs 26.9 ± 0.3 [weeks ± SE], p = 0.03) and birth weight ([Bwt]; 1080 ± 48.8 vs 899 ± 45.8 [grams ± SE], p = 0.01) between groups. Significantly fewer PBs in the fast group had a patent ductus arteriosus (PDA) compared to the slow group (5/26 (19.2%) vs 13/24 (54.2 %), p = 0.02). Bwt was a significant negative predictor of CPAP duration (r = -0.497, p = 0.03) and CPAP ceasing attempts (r = -0.290, p = 0.04). CONCLUSION: PBs with a higher GA and Bwt without a PDA ceased CPAP earlier using the CICADA method. Bwt was better than GA for predicting CPAP duration and attempts to cease CPAP. WHAT IS KNOWN: Our previous studies showed that CeasIng Cpap At standarD criteriA (CICADA) significantly reduces CPAP time, oxygen requirements and caffeine use. Some PBs however using the CICADA method required >2 attempts to cease CPAP ('slow CICADA' group). WHAT IS NEW: PBs in the 'fast CICADA' group (<3 attempts to cease CPAP) (a) have longer gestational age and higher birth weight, (b) shorter mechanical ventilation and (c) lower incidence of patent ductus arteriosus. Attempts to cease CPAP decreased by 0.5 times per 1 week increase in GA and 0.3 times per 100-g increase in birth weight for PBs <30 weeks gestation.

CeasIng Cpap At standarD criteriA (CICADA): Implementation improves neonatal outcomes.

BACKGROUND: A previous randomised controlled trial (RCT) in babies born < 30 weeks gestation found the so-called CICADA method (ceasing continuous positive airways pressure (CPAP) with a view to remain off rather than slow weaning) significantly reduced CPAP time. Post-RCT we introduced the CICADA method and evaluated whether the improved outcomes of the CICADA method during the RCT were replicated in clinical practice. AIM: The aim of the study is to compare cardio-respiratory outcomes in PBs < 30 weeks GA over three epochs: (i) pre RCT, (ii) during RCT and (iii) post RCT implementation. METHODS: The study used prospective data to compare baseline characteristics and cardio-respiratory outcomes over the three epochs. RESULTS: There were 270/393(69%) PBs < 30 weeks GA who fulfilled the inclusion criteria over the three epochs. No significant differences were found in GA or birthweight between the three epochs (27.9 ± 1.3, 27.7 ± 1.4, 28.0 ± 1.3 (weeks ± 1 standard deviation); and 1100 ± 252, 1086 ± 251, 1094 ± 320 (grams ± 1 standard deviation)). There were significant decreases in CPAP days and corrected GA to cease CPAP post implementation (20.5 ± 2.1, 21.1 ± 2.1, 16.5 ± 1.8 (days ± SE); P = 0.006 and 33.3 ± 0.4, 33.5 ± 0.4, 32.6 ± 0.4 (weeks ± SE); P = 0.01). Compared with the pre RCT epoch, there were significant reductions in patent ductus arteriosus (36/78 (46%), 33/87 (37%), 18/103 (17%); P < 0.001) and chronic lung disease (40/78 (51%), 19/87 (21%), 30/103 (29%); P < 0.001). CONCLUSIONS: CPAP time, corrected GA to cease CPAP, patent ductus arteriosus and chronic lung disease significantly reduced following the introduction of the CICADA method. Early cessation of CPAP expedites the transition from neonatal intensive care to special care.

Tongue-tie in the newborn: Follow-up in the first 6 months.

BACKGROUND: Over the last decade, a number of studies have demonstrated that early division of tongue-tie (TT) is associated with significant feeding benefits to both mother and baby. Notwithstanding, it remains a controversial procedure. We examined the breastfeeding outcomes of a cohort of babies at 1-2 weeks (follow-up 1) and 3-5 months (follow-up 2), post-TT division. METHODS: We undertook a cohort study on all mother/baby dyads who had a TT divided at Canberra Hospital between 1 July 2013 and 30 June 2014. We contacted the mothers of both follow-up groups by telephone, focusing on breastfeeding and maternal pain. RESULTS: Follow-up 1 consisted of 116/182 (63.7%) of mothers in the study; contacted at 12.4+-7.8 days post-division. Of these, 107/116 (92.2%) were still breastfeeding, with 11/15 (73.3%) of the mothers who had ceased breastfeeding before division having re-established it at the time of follow-up (p < 0.00l). Additionally, 90/101 (89.1%) valid responses reported decreased nipple pain following TT division. Follow-up 2 consisted of 112/182 (61.5%) of all mothers in the study; contacted at 3.7+-1.8 months of age. Of these, 86/112 (76.8%) were still breastfeeding, with 11/15 (73.3%) of mothers who had ceased breastfeeding before division having re-established it at follow-up (p < 0.001). CONCLUSION: A divided TT was associated with benefits at both periods of follow-up. There was (i) an increase in overall breastfeeding rates and (ii) a decrease in maternal pain.

Respiratory outcomes study (RESPOS) for preterm infants at primary school age.

OBJECTIVE: Pulmonary function abnormalities and hospital re-admissions in survivors of neonatal lung disease remain highly prevalent. The respiratory outcomes study (RESPOS) aimed to investigate the respiratory and associated atopy outcomes in preterm infants <30 weeks gestational age (GA) and/or birth-weight (BWt) <1000 g at primary school age, and to compare these outcomes between infants with and without chronic lung disease (CLD). METHODS: In the RESPOS 92 parents of preterm infants admitted to the Neonatal unit in Canberra Hospital between 1/1/2001 and 31/12/2003 were sent a questionnaire regarding their respiratory, atopy management and follow-up. RESULTS: Fifty-three parents responded, including 28 preterm infants who had CLD and 25 who had no CLD. The gestational age was significantly lower in the CLD group compared to the non-CLD group [26.9 (26.3-27.5) CLD and 28.6 (28.3-29.0) non-CLD] [weeks [95% confidence interval (CI)]], as was the birth weight [973 (877.4-1068.8) CLD versus 1221 (1135.0-1307.0) non-CLD] [g (CI)]. CLD infants compared to non-CLD infants were significantly more likely to have been: given surfactant, ventilated and on oxygen at 28 days and 36 weeks. These neonates were also more likely to have: been discharged from the neonatal unit on oxygen, exhibit a history of PDA or sepsis and to have a current paediatrician. However, despite these differences, there was no significant difference in the proportion of asthma or atopic disease between the two groups. CONCLUSIONS: The RESPOS could not demonstrate respiratory and/or atopy differences between the CLD and the non-CLD groups at primary school age.

Shorter ischaemic time and improved survival with pre-hospital STEMI diagnosis and direct transfer for primary PCI.

BACKGROUND: We sought to determine if our regional program for pre-hospital STEMI diagnosis and direct transfer for primary PCI (PPCI) was associated with shorter ischaemic times and improved survival compared with ED diagnosis. METHODS: STEMI diagnosis was made at the scene by pre-hospital ECG or in local EDs depending on patient presentation. Ambulance ECGs were transmitted to our ED for cath lab activation. Patient variables and outcomes at 12 months were recorded. RESULTS: We treated 782 consecutive patients with PPCI during January 2008-June 2013. Cath lab activation was initiated prior to hospital arrival (pre-hospital) in 24% of cases and by ED in 76% of cases. Median total ischaemic time was 154 min for pre-hospital and 211 minutes for ED patients (p<0.0001). Mortality at 12 months was 7.9% in the ED group compared with 3.7% in the pre-hospital group (p=0.036). On multivariate Cox regression analysis including baseline and procedural variables, pre-hospital activation remained an independent predictor of mortality (HR 0.45, 95% CI 0.20-1.0, p=0.03). CONCLUSIONS: Pre-hospital diagnosis of STEMI and direct transfer to the cath lab reduced total ischaemic time by 57 minutes and mortality by >50% following PPCI. Further efforts are needed to increase the proportion of STEMI patients treated using this strategy.

Influence of psychiatric diagnosis on treatment uptake and interferon side effects in patients with hepatitis C.

BACKGROUND AND AIM: Pegylated-interferon-α/ribavirin (PEG-IFN/RBV) treatment can cure hepatitis C virus (HCV) infection but has frequent neuropsychiatric side-effects. Patients with pre-existing psychiatric illness may not be offered therapy. We established prevalence of self-reported psychiatric comorbidity among HCV-infected patients in a hospital-liver clinic, and determined the impact of such diagnoses on uptake and tolerance to PEG-IFN/RBV. METHODS: All HCV cases referred for assessment in Australian Capital Territory/surrounding regions April 2004-March 2012 were entered into a clinical database. We conducted univariate and multivariate analyses of variables correlating with uptake of antiviral therapy and frequency of treatment-related side-effects. RESULTS: Of 773 referred patients, 235 (30%) described pre-existing psychiatric illness. Among these, 26% received antiviral therapy, compared with 30% of 538 without psychiatric comorbidity. History of depression (usually validated by liaison psychiatry) was associated with higher incidence of treatment-related neuropsychiatric side-effects (odds ratio 2.79 [1.35-5.70], P < 0.05) but did not affect treatment outcome. Twenty-seven patients reported schizophrenia: three (11%) received antiviral therapy, compared with 30% admitting depression and 20% with bipolar affective disorder (all assessed by psychiatrist). In most schizophrenia cases, the reason for not offering antiviral treatment was psychological illness, yet none of five treated (these three plus two others in a psychiatric rehabilitation facility) experienced worsening psychiatric symptoms. CONCLUSIONS: A history of depression is common with hepatitis C but does not affect initiation of antiviral treatment, despite substantially increased risk of psychiatric side-effects. In contrast, pre-existing schizophrenia appears to influence treatment decisions, despite little evidence that PEG-IFN/RBV exacerbates the psychiatric condition, and well-supervised antiviral therapy can have good outcomes.

Improved Outcome With Knee Arthroscopy Relative to Physiotherapy for Symptomatic Unstable Meniscal Tears: 2-Year Prospective Cohort Study.

BACKGROUND: Although preservation of meniscal tissue is paramount, there are occasions when repair of a torn meniscus is not possible. The surgical option may be a partial meniscectomy, the objective being to alleviate the patient's symptoms with resection of only that portion of the meniscus that is no longer functioning but is the cause of symptoms. Previous studies have questioned the need to perform such surgery and have recommended nonoperative treatment instead. Our goal was to compare the outcome of partial meniscectomy with that of physiotherapy alone for irreparable meniscal tears. HYPOTHESIS: Clinical outcome following arthroscopic partial meniscectomy may differ from that following physiotherapy alone, for patients with symptomatic irreparable meniscal tears. STUDY DESIGN: Nonrandomized prospective cohort study. LEVEL OF EVIDENCE: Level 2. METHODS: Patients satisfying the inclusion criteria chose to undergo knee arthroscopy (group A) or physiotherapy (group B). The diagnosis of a meniscal tear was made on physical assessment and magnetic resonance imaging examination. The meniscal tear was preventing them from continuing with their regular weightbearing exercise. Outcomes of interest were the following patient-reported outcomes (PROs): the Knee Osteoarthritis Outcome Score (KOOS) and Tegner Activity Score (TAS), with minimal clinically important differences being 10 and 1, respectively. PROs were completed at baseline, and at 1-year and 2-year follow-up. Changes in scores within and between groups were compared using analysis of variance and Wilcoxon tests (P <0.05). A power analysis demanded 65 patients in each group to produce a power of 80% and a P value of 5%. RESULTS: Of 528 patients enrolled in the study, 10 were lost to follow-up and 8 were excluded. Data were complete for 269 in group A, and 228 in Group B. Group A and B were similar in terms of age (41.1 years, SD 7.8 vs 40 years, SD 13.3), body mass index (22.5 kg/m2, SD 3.1 vs 23.1 kg/m2, SD 2.3), radiographic grade of osteoarthritis (median grade 2, range 0-3 in both groups), gender (male:female = 134:135 vs 112:116), and duration of symptoms (44.4 days, SD 5.6 vs 46.6 days, SD 8.8), with P >0.05. At both 1-year and 2-year follow-up, Group A had higher scores in the mean total KOOS (88.8, SD 8.0 vs 72.4, SD 3.8), as well as in all subscales within the KOOS, and the TAS (median 7, range 5-9 vs median 5, range 3-6), with P <0.001 for each variable. CONCLUSION: Performing a knee arthroscopy with partial meniscectomy is associated with improved KOOS and TAS, relative to treatment with physiotherapy alone, at 2-year follow-up. CLINICAL RELEVANCE: Physically active patients with symptomatic irreparable meniscal tears may experience a better clinical outcome following knee arthroscopy, relative to to physiotherapy alone.

Diastolic function is a strong predictor of mortality in patients with chronic kidney disease.

BACKGROUND: Cardiovascular disease is a major cause of death in patients with stage 4-5 Chronic Kidney disease (CKD, eGFR < 30). There are only limited data on the risk factors predicting these complications in CKD patients. Our aim was to determine the role of clinical and echocardiographic parameters in predicting mortality and cardiovascular complications in CKD patients. METHODS: We conducted a prospective observational cohort study of 153 CKD patients between 2007 and 2009. All patients underwent echocardiography at baseline and were followed for a mean of 2.6 years using regular clinic visits and review of files and hospital presentations to record the incidence of cardiovascular events and death. RESULTS: Of 153 patients enrolled, 57 (37%) were on dialysis and 45 (78%) of these patients were on haemodialysis. An enlarged LV was present in 32% of patients and in 22% the LVEF was below 55%. LV mass index was increased in 75% of patients. Some degree of diastolic dysfunction was present in 85% of patients and 35% had grade 2 or higher diastolic dysfunction. During follow up 41 patients (27%) died, 15 (39%) from cardiovascular causes. Mortality was 24.0% in the non-dialysis patients versus 31.6% in patients on dialysis (p=ns). On multivariate analysis age >75 years, previous history of MI, diastolic dysfunction and detectable serum troponin T were significant independent predictor of mortality (P < 0.01). CONCLUSION: Patients with stage 4-5 CKD had a mortality rate of 27% over a mean follow up of 2.6 years. Age >75 years, history of MI, diastolic dysfunction and troponin T were independent predictors of mortality.

Inspired gas humidity and temperature during mechanical ventilation with the Stephanie ventilator.

AIMS: To measure inspired gas humidity and temperature delivered by a Stephanie neonatal ventilator with variations in (i) circuit length; (ii) circuit insulation; (iii) proximal airway temperature probe (pATP) position; (iv) inspiratory temperature (offset); and (v) incubator temperatures. METHODS: Using the Stephanie neonatal ventilator, inspired gas humidity and temperature were measured during mechanical ventilation at the distal inspiratory limb and 3 cm down the endotracheal tube. Measurements were made with a long or short circuit; with or without insulation of the inspiratory limb; proximal ATP (pATP) either within or external to the incubator; at two different inspiratory temperature (offset) of 37(-0.5) and 39(-2.0)°C; and at three different incubator temperatures of 32, 34.5, and 37°C. RESULTS: Long circuits produced significantly higher inspired humidity than short circuits at all incubator settings, while only at 32°C was the inspired temperature higher. In the long circuits, insulation further improved the inspired humidity especially at 39(-2.0)°C, while only at incubator temperatures of 32 and 37°C did insulation significantly improve inspired temperature. Positioning the pATP outside the incubator did not result in higher inspired humidity but did significantly improve inspired temperature. An inspiratory temperature (offset) of 39(-2.0)°C delivered significantly higher inspired humidity and temperature than the 37(-0.5)°C especially when insulated. CONCLUSIONS: Long insulated Stephanie circuits should be used for neonatal ventilation when the infant is nursed in an incubator. The recommended inspiratory temperature (offset) of 37(-0.5)°C produced inspired humidity and temperature below international standards, and we suggest an increase to 39(-2.0)°C.

Diffuse large B-cell lymphoma and red cell autoimmunity: clinical role and pathogenesis.

Diffuse large B-cell lymphoma (DLBCL) is the most common form of B-cell non-Hodgkin lymphoma (B-NHL) with significant morbidity and mortality despite advancements in treatment. Lymphoma and autoimmune disease both result from breakdowns in normal cell regulatory pathways, and epidemiological studies have confirmed both that B-NHL is more likely to develop in the setting of autoimmune diseases and vice versa. Red cell immunity, as evidenced by direct antiglobulin test (DAT) positivity, has been linked to DLBCL and more recently the pathogenic causes of this association have begun to be better understood using molecular techniques. This project aimed to explore the relationship between red cell autoimmunity and DLBCL. DAT positivity was more common in DLBCL as compared to healthy controls (20.4% vs 3.7%, p=0.0005). Univariate analysis found a non-significant trend towards poorer overall survival in the DAT positive (DAT+) compared to the DAT negative (DAT-) groups (p=0.087). High throughput sequencing was used to compare mutations in DLBCL from DAT+ and DAT- patients. The most frequently mutated genes in 15 patient samples were KMT2D (n=13), MYOM2 (n=9), EP300 (n=8), SPEN (n=7), and ADAMTSL3 (n=7), which were mutated in both DAT+ and DAT- groups. BIRC3 (n=3), FOXO1 (n=3) and CARD11 (n=2) were found to be mutated only in samples from the DAT+ group. These gene mutations may be involved in disease development and progression, and potentially represent targets for future therapy. The immunoglobulin genotype IGHV4-34 is seen more frequently in DLBCL clones than in normal B cells and has intrinsic autoreactivity to self-antigens on red cells, which is largely mediated by two motifs within the first framework region (FR1); Q6W7 and A24V25Y.26 These motifs form a hydrophobic patch which determines red cell antigen binding and are frequently mutated away from self-reactivity in normal B cells. If this does not occur this may provide constant B cell receptor signalling which encourages lymphoma development, a theory known as antigen driven lymphomagenesis. As with previous studies, IGHV4-34 was over-represented (15.6%) in our DLBCL cohort. Furthermore, of 6 IGHV4-34-expressing DLBCL samples five had unmutated hydrophobic patch mutations providing further evidence for antigen-driven lymphomagenesis. Mutation analysis of these five samples demonstrated high frequency of mutations in several genes, including CREBBP and NCOR2. Further research could explore if mutations in CREBBP and NCOR2 work in conjunction with the preserved QW and AVY motifs to promote lymphomagenesis in IGHV4-34-expressing B cells, and if so, could guide future targeted therapy.

Precision of histological bone marrow staging in follicular lymphoma and diffuse large B-cell lymphoma.

INTRODUCTION: In Non-Hodgkin Lymphoma (NHL), bone marrow histology is the gold standard against which ancillary investigations such as immunophenotyping and gene rearrangement studies are interpreted. There is currently no data on the reproducibility of histological findings. This study was conducted to determine the rates of inter- and intra-observer agreement in histological detection of bone marrow involvement in the two major subtypes of NHL, Diffuse Large B-cell Lymphoma (DLBCL), and Follicular Lymphoma (FL). METHODS: The bone marrow slides of randomly selected DLBCL and FL cases were independently examined by two hematologists using standardized reporting criteria on two occasions at least two weeks apart. Samples included both aspirate and trephine biopsy slides. Weighted kappa statistics were used to examine agreement for the discrete measures. RESULTS: Weighted kappa analyses showed variable inter-observer agreement in 38 DLBCL cases [aspirate=0.52; trephine= 0.77] and 38 FL cases [aspirate=0.48; trephine=0.77]. CONCLUSION: Overall, higher agreement rates were noted with trephine biopsies than with aspirates. Except for the high intra-observer agreement on trephine biopsy assessment in FL, there is poor agreement in histological staging of both FL and DLBCL which demonstrates the limitations of histological diagnosis and the futility of interpreting ancillary tests against histology.

Trajectories of long-term outcomes for postnatally depressed mothers treated with group interpersonal psychotherapy.

There is evidence that psychological treatments for postnatal depression are effective in the short-term; however, whether the effects are enduring over time remains an important empirical question. The aim of this study was to investigate the depressive symptoms and interpersonal functioning of participants in a randomised controlled trial (RCT) of group interpersonal psychotherapy (IPT-G) at 2 years posttreatment. The study also examined long-term trajectories, such as whether participants maintained their recovery status, achieved later recovery, recurrence or persistent symptoms. Approximately 2 years posttreatment, all women in the original RCT (N = 50) were invited to participate in a mailed follow-up. A repeated measures analysis of variance assessed differences between the treatment and control conditions on depression and interpersonal scores across five measurement occasions: baseline, mid-treatment, end of treatment and 3-month and 2-year follow-up. Chi-square tests were used to analyse the percentage of participants in the four recovery categories. Mothers who received IPT-G improved more rapidly in the short-term and were less likely to develop persistent depressive symptoms in the long-term. Fifty seven percent of IPT-G mothers maintained their recovery over the follow-up period. Overall, IPT-G participants were significantly less likely to require follow-up treatment. Limitations include the use of self-report questionnaires to classify recovery. The positive finding that fewer women in the group condition experienced a persistent course of depression highlights its possible enduring effects after treatment discontinuation. Further research is needed to improve our long-term management of postnatal depression for individuals who are vulnerable to a recurrent or chronic trajectory.